TFE3 antibody is a crucial diagnostic tool used in pathology to detect neoplasms associated with TFE3 gene rearrangements. TFE3. a member of the MiT family of transcription factors, regulates cellular processes like proliferation and lysosome biogenesis. In normal tissues, TFE3 expression is low, but specific chromosomal translocations (e.g., Xp11.2 or t(6;11)(p21;q13)) can lead to TFE3 fusion proteins that drive tumorigenesis. These genetic alterations are hallmark features of certain cancers, including Xp11.2 translocation renal cell carcinoma, alveolar soft part sarcoma (ASPS), and a subset of perivascular epithelioid cell tumors (PEComas).
Immunohistochemistry (IHC) using TFE3 antibodies helps identify nuclear overexpression of TFE3 protein, supporting the diagnosis of these tumors. However, interpretation requires caution, as weak or nonspecific staining may occur in non-neoplastic tissues or other malignancies. False positives can arise due to technical factors or cross-reactivity with related MiT family proteins (e.g., MITF). Thus, TFE3 IHC is typically combined with molecular confirmation (FISH, RNA sequencing) for definitive diagnosis.
The antibody’s clinical utility lies in distinguishing TFE3-rearranged tumors from histologic mimics, guiding treatment decisions, and enabling research into targeted therapies. Its role underscores the integration of molecular pathology into modern diagnostic workflows.